The vast majority of cocaine abusers, including those enrolled in drug abuse treatment, regularly use and abuse other drugs. Unfortunately, little scientific information is available indicating how such other drug use and abuse may influence the probability of cocaine use. This absence of information prevents clinicians from making empirically-based recommendations regarding the likely influence of other drug use on the course of cocaine abuse. The purpose of the research proposed in this application is to begin to address this important issue by experimentally analyzing the influence of other drug use on cocaine self-administration in humans under controlled laboratory conditions. Study 1 will be devoted to establishing an effective laboratory model for assessing the influence of drug pretreatment on cocaine self- administration. Intranasal doses of cocaine and varying amounts of money will be available under concurrent fixed-ratio schedules of reinforcement. The influence of the amount of money available via the alternate option on cocaine self-administration will be assessed. Using the parametric information obtained in Study 1, cocaine availability in Studies 2-5 will be scheduled under conditions supporting relatively high, intermediate, and near-zero levels of cocaine self-administration. Respectively, those studies will assess the acute effects of pretreatment with varying doses of alcohol (0, 0.5, & 1.0 g/kg), marijuana (0, 1.3, & 2.7% delta9-THC/cigarette), caffeine (0, 150, 300 mg/70 kg) and nicotine (0.14, 1.14, & 2.20 mg/cigarette) on cocaine self-administration occurring at each of those three different levels. By systematically varying both the baseline level of cocaine self-administration and dose of the pretreatment drugs, a comprehensive analysis will be provided. Detection of drug-produced increases or decreases in cocaine use should be discernible. These studies will provide novel and important information that should be useful (1) in understanding drug interactions, (2) in understanding how other drug use may alter the relative control exerted by cocaine versus an alternative, non-drug reinforcer, and, most importantly, (3) in developing effective, empirically-based treatment strategies for achieving and maintaining cocaine abstinence.